Biopolym. Cell. 1998; 14(3):210-222.
http://dx.doi.org/10.7124/bc.0004D0
Клітинна біологія
Сигнальні молекули у регенеруючій печінці
1Оболенська М. Ю.
  1. Інститут молекулярної біології і генетики НАН України
    Вул. Академіка Заболотного, 150, Київ, Україна, 03680

Abstract

Роботу присвячено дослідженню відповідності у часі та можливому причинно-наслідковому зв'язку між утворенням сигнальних молекул і біохімічними процесами, що проходять у регенеруючій печінці після часткової гепатектомй. Події клітинних циклів гепатоцитів і синусоїдальних клітин, починаючих проліферувати у певній послідовності, використовували як маркери часової шкали регенераційного процесу. Сигнальні молекули регенеруючої печінки, які представлені цитокінами, похідними арахідонової кислоти та неорганічними молекулами типу окису азоту, регулюють функціональну активність одне одного та утворюють єдину систему міжклітинної взаємодії, пo кількості і набору елементів характерну для кожного періоду відновлювального процесу. Перехід печінки від стану спокою до клітинного ділення з первинним притягненням до проліферації гепатоцитів активно регулюється сигнальними молекулами, утвореними синусоїдальними клітинами. Проліферація останніх супроводжується зниженням їхньої паракринної активності. Зроблено припущення стосовно антагонізму клітиноспецифічної і проліферативної активності у рамках одного типу клітин та щодо їхнього синергізму у клітинах різного типу, а також про існування для кожного типу клітин печінки клітиноспецифічних мітогенів, які одночасно пригнічують синтез ДНК у клітинах іншого типу.
Повний текст: (PDF, російською)

References

[1] Liozner LD. Regeneration and Development. M., Nauka, 1982. 167 p.
[2] Tsanev R. Cell cycle and liver function. Results and Problems in Cell Differentiation. Berlin etc.: Springer, 1975: 197-248.
[3] Wilson JW, Groat CS, Leduc EH. Histogenesis of the liver. Ann N Y Acad Sci. 1963;111:8-24.
[4] Douarin NM. An experimental analysis of liver development. Med Biol. 1975;53(6):427-55.
[5] Birchmeier C, Birchmeier W. Molecular aspects of mesenchymal-epithelial interactions. Annu Rev Cell Biol. 1993;9:511-40.
[6] Higgins GM, Anderson RM. Experimental pathology of the liver. Arch Pathol. 1931; 12: 186-202.
[7] Nathan C, Sporn M. Cytokines in context. J Cell Biol. 1991;113(5):981-6.
[8] Koch KS, Lu XP, Brenner DA, Fey GH, Martinez-Conde A, Leffert HL. Mitogens and hepatocyte growth control in vivo and in vitro. In Vitro Cell Dev Biol. 1990;26(11):1011-23.
[9] Michalopoulos GK. Liver regeneration: molecular mechanisms of growth control. FASEB J. 1990;4(2):176-87.
[10] Andus T, Bauer J, Gerok W. Effects of cytokines on the liver. Hepatology. 1991;13(2):364-75.
[11] Fausto N, Webber E. Liver regeneration. The Liver: Biology and Pathobiology. Eds I. M. Arias et al. New York: Raven press. 1994; 1059-1084.
[12] Fausto N, Laird AD, Webber EM. Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration. FASEB J. 1995;9(15):1527-36.
[13] Gerok W. Grundprozesse der Leberpathologie. Hepatologie. Eds W. Gerok, H. E. Blum. Munchen-Wien-Baltimore: Urban et Schwarzenberg; 1995: 72-93.
[14] Steer CJ. Liver regeneration. FASEB J. 1995;9(14):1396-400.
[15] Diehl AM, Rai RM. Liver regeneration 3: Regulation of signal transduction during liver regeneration. FASEB J. 1996;10(2):215-27.
[16] Taub R. Liver regeneration 4: transcriptional control of liver regeneration. FASEB J. 1996;10(4):413-27.
[17] Decker K. Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem. 1990;192(2):245-61.
[18] Marletta MA. Mammalian synthesis of nitrite, nitrate, nitric oxide, and N-nitrosating agents. Chem Res Toxicol. 1988;1(5):249-57.
[19] Curran RD, Billiar TR, Stuehr DJ, Hofmann K, Simmons RL. Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells. J Exp Med. 1989;170(5):1769-74.
[20] Billiar TR, Curran RD, Stuehr DJ, West MA, Bentz BG, Simmons RL. An L-arginine-dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. J Exp Med. 1989;169(4):1467-72.
[21] Gaillard T, M?lsch A, Busse R, Klein H, Decker K. Regulation of nitric oxide production by stimulated rat Kupffer cells. Pathobiology. 1991;59(4):280-3.
[22] Feder LS, Laskin DL. Regulation of hepatic endothelial cell and macrophage proliferation and nitric oxide production by GM-CSF, M-CSF, and IL-1 beta following acute endotoxemia. J Leukoc Biol. 1994;55(4):507-13.
[23] Heylar L, Bundschuh DS, Laskin JD, Laskin IX L. Hepatic fat storing cells produce nitic oxide and hydrogen peroxide in response to bacterially-derived lipopolysacchride (LPS). Cells of the Hepatic Sinusoid. Eds. D. L. Knook, E. Wisse. Leiden: The Kupffer Cell Foundation, 1993; Vol. 4: 67-9.
[24] Grisham JW. A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver; autoradiography with thymidine-H3. Cancer Res. 1962;22:842-9.
[25] Widmann JJ, Fahimi HD. Proliferation of mononuclear phagocytes (Kupffer cells) and endothelial cells in regenerating rat liver. A light and electron microscopic cytochemical study. Am J Pathol. 1975;80(3):349-66.
[26] Tanaka Y, Mak KM, Lieber CS. Immunohistochemical detection of proliferating lipocytes in regenerating rat liver. J Pathol. 1990;160(2):129-34.
[27] Bucher NL, Swaffield MN. The rate of incorporation of labeled thymidine into the deoxyribonucleic acid of regenerating rat liver in relation to the amount of liver excised. Cancer Res. 1964;24:1611-25.
[28] Stocker E. Alterabhaengige zellproliferationskinetik und Regenerationkapazitaet im Leberepithel der Ratlc. Actuelle Gerontologie. 1971. 1: 559-665.
[29] Obolenskaya MYu, Prima VI, Gerasimova TB, Platonov OM. Partial restriction of genome expression – a component of its work reprogramming in regenerating liver of mammals. Biopolym Cell. 1989; 5(2):79-88.
[30] Hochachka PW, Somero GN. Strategies of biochemical adaptation. WB. Saunders Company (Ed.), Philadelphia, London, Toronto. 1973 358 p.
[31] Mohn KL, Laz TM, Hsu JC, Melby AE, Bravo R, Taub R. The immediate-early growth response in regenerating liver and insulin-stimulated H-35 cells: comparison with serum-stimulated 3T3 cells and identification of 41 novel immediate-early genes. Mol Cell Biol. 1991;11(1):381-90.
[32] Flodby P, Antonson P, Barlow C, Blanck A, Porsch-H?llstr?m I, Xanthopoulos KG. Differential patterns of expression of three C/EBP isoforms, HNF-1, and HNF-4 after partial hepatectomy in rats. Exp Cell Res. 1993;208(1):248-56.
[33] Mischoulon D, Rana B, Bucher NL, Farmer SR. Growth-dependent inhibition of CCAAT enhancer-binding protein (C/EBP alpha) gene expression during hepatocyte proliferation in the regenerating liver and in culture. Mol Cell Biol. 1992;12(6):2553-60.
[34] Lu XP, Koch KS, Lew DJ, Dulic V, Pines J, Reed SI, Hunter T, Leffert HL. Induction of cyclin mRNA and cyclin-associated histone H1 kinase during liver regeneration. J Biol Chem. 1992;267(5):2841-4.
[35] Martinez-Hernandez A, Amenta PS. The extracellular matrix in hepatic regeneration. FASEB J. 1995;9(14):1401-10.
[36] Miura Y, Fukui N. Prostaglandins as possible triggers for liver regeneration after partial hepatectomy. A review. Cell Mol Biol Incl Cyto Enzymol. 1979;25(3):179-84.
[37] Decker K. The regulatory role of prostaglandins in the challenged liver. Lipid Mediators in Health and Disease. Ed. U. Zor. New York: Freund Publ. House, Ltd., 1994: 133-137.
[38] Kawada N, Decker K. On the contraction and relaxation of stellate cells induced by Kupffer cell-derived vasoactive substances. Cytokines and the liver. Eds W. Gerok et al. Dordrecht etc.: Kluwer Acad, publ., 1995: 83-92.
[39] Fisher RA, Robertson SM, Olson MS. Stimulation of glycogenolysis and vasoconstriction in the perfused rat liver by the thromboxane A2 analogue U-46619. J Biol Chem. 1987;262(10):4631-8.
[40] Becker FF. Acute glycogenolysis: a major stimulus of autophagocytic activity in rat hepatocytes. 1. Proc Soc Exp Biol Med. 1972;140(4):1170-2.
[41] MacManus JP, Braceland BM. A connection between the production of prostaglandins during liver regeneration and the DNA synthetic response. Prostaglandins. 1976;11(4):609-20.
[42] Callery MP, Mangino MJ, Flye MW. Kupffer cell prostaglandin-E2 production is amplified during hepatic regeneration. Hepatology. 1991;14(2):368-72.
[43] H?ussinger D, Stehle T, Tran-Thi TA, Decker K, Gerok W. Prostaglandin responses in isolated perfused rat liver: Ca2+ and K+ fluxes, hemodynamic and metabolic effects. Biol Chem Hoppe Seyler. 1987;368(11):1509-13.
[44] Melien O, Winsnes R, Refsnes M, Gladhaug IP, Christoffersen T. Pertussis toxin abolishes the inhibitory effects of prostaglandins E1, E2, I2 and F2 alpha on hormone-induced cAMP accumulation in cultured hepatocytes. Eur J Biochem. 1988;172(2):293-7.
[45] Fausto N, Butcher FR. Cyclic nucleotide levels in regenerating liver. Biochim Biophys Acta. 1976;428(3):702-6.
[46] Refsnes M, Thoresen GH, Dajani OF, Christoffersen T. Stimulation of hepatocyte DNA synthesis by prostaglandin E2 and prostaglandin F2 alpha: additivity with the effect of norepinephrine, and synergism with epidermal growth factor. J Cell Physiol. 1994;159(1):35-40.
[47] Obolenskaya MYu, Bernauer H, Tran-Thi T-A, Decker K. Levels of rna for TNF-? and receptors during the prereplicative period of liver regeneration. Biopolym Cell. 1994; 10(5):68-77.
[48] Decker KF, Obolenskaya MY. Cytokines, nitric oxide synthesis and liver regeneration. J Gastroenterol Hepatol. 1995;10 Suppl 1:S12-7.
[49] Trautwein C, Rakemann T, Niehof M, Rose-John S, Manns MP. Acute-phase response factor, increased binding, and target gene transcription during liver regeneration. Gastroenterology. 1996;110(6):1854-62.
[50] Yamada Y, Kirillova I, Peschon JJ, Fausto N. Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. Proc Natl Acad Sci U S A. 1997;94(4):1441-6.
[51] Mochida S, Ohta Y, Ogata I, Fujiwara K. Gut-derived substances in activation of hepatic macrophages after partial hepatectomy in rats. J Hepatol. 1992;16(3):266-72.
[52] Fisher B, Gebhardt MC, Saffer EA, Fisher ER. Effect of Corynebacterium parvum on liver proliferation and regeneration. Cancer Res. 1979;39(4):1361-8.
[53] Cornell RP. Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration. Am J Physiol. 1985;249(5 Pt 2):R563-9.
[54] Vlassara H, Brownlee M, Manogue KR, Dinarello CA, Pasagian A. Cachectin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. Science. 1988;240(4858):1546-8.
[55] Drouet C, Shakhov AN, Jongeneel CV. Enhancers and transcription factors controlling the inducibility of the tumor necrosis factor-alpha promoter in primary macrophages. J Immunol. 1991;147(5):1694-700.
[56] Freedman AR, Sharma RJ, Nabel GJ, Emerson SG, Griffin GE. Cellular distribution of nuclear factor kappa B binding activity in rat liver. Biochem J. 1992;287 ( Pt 2):645-9.
[57] Tran-Thi TA, Decker K, Baeuerle PA. Differential activation of transcription factors NF-kappa B and AP-1 in rat liver macrophages. Hepatology. 1995;22(2):613-9.
[58] Akerman P, Cote P, Yang SQ, McClain C, Nelson S, Bagby GJ, Diehl AM. Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. Am J Physiol. 1992;263(4 Pt 1):G579-85.
[59] Vilfek J, Palombella V. TNF as a growth factor. Tumor necrosis factor. Eds B. B. Aggarwal, J. Vilcek. New York: Basel; Hong Kong: Marcell Dekker, Inc., 1992: 269-88.
[60] Satoh M, Yamazaki M. Tumor necrosis factor stimulates DNA synthesis of mouse hepatocytes in primary culture and is suppressed by transforming growth factor beta and interleukin 6. J Cell Physiol. 1992;150(1):134-9.
[61] Matsuoka M, Pham NT, Tsukamoto H. Differential effects of interleukin-1 alpha, tumor necrosis factor alpha, and transforming growth factor beta 1 on cell proliferation and collagen formation by cultured fat-storing cells. Liver. 1989;9(2):71-8.
[62] Beyer HS, Stanley M. Tumor necrosis factor-alpha increases hepatic DNA and RNA and hepatocyte mitosis. Biochem Int. 1990;22(3):405-10.
[63] Feingold KR, Barker ME, Jones AL, Grunfeld C. Localization of tumor necrosis factor-stimulated DNA synthesis in the liver. Hepatology. 1991;13(4):773-9.
[64] Columbano A, Shinozuka H. Liver regeneration versus direct hyperplasia. FASEB J. 1996;10(10):1118-28.
[65] Kalthoff H, Roeder C, Brockhaus M, Thiele HG, Schmiegel W. Tumor necrosis factor (TNF) up-regulates the expression of p75 but not p55 TNF receptors, and both receptors mediate, independently of each other, up-regulation of transforming growth factor alpha and epidermal growth factor receptor mRNA. J Biol Chem. 1993;268(4):2762-6.
[66] Rothe M, Wong SC, Henzel WJ, Goeddel DV. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell. 1994;78(4):681-92.
[67] Tamura M, Arakaki N, Tsubouchi H, Takada H, Daikuhara Y. Enhancement of human hepatocyte growth factor production by interleukin-1 alpha and -1 beta and tumor necrosis factor-alpha by fibroblasts in culture. J Biol Chem. 1993;268(11):8140-5.
[68] Hoffmann R, Henninger HP, Schulze-Specking A, Decker K. Regulation of interleukin-6 receptor expression in rat Kupffer cells: modulation by cytokines, dexamethasone and prostaglandin E2. J Hepatol. 1994;21(4):543-50.
[69] Str?mblad S, Andersson G. The coupling between transforming growth factor-alpha and the epidermal growth factor receptor during rat liver regeneration. Exp Cell Res. 1993;204(2):321-8.
[70] Matsumoto K, Nakamura T. Hepatocyte growth factor: molecular structure and implications for a central role in liver regeneration. J Gastroenterol Hepatol. 1991;6(5):509-19.
[71] Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V, Taub R. Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science. 1996;274(5291):1379-83.
[72] Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992;6(12):3051-64.
[73] Curran RD, Billiar TR, Stuehr DJ, Ochoa JB, Harbrecht BG, Flint SG, Simmons RL. Multiple cytokines are required to induce hepatocyte nitric oxide production and inhibit total protein synthesis. Ann Surg. 1990;212(4):462-9.
[74] Geller DA, de Vera ME, Russell DA, Shapiro RA, Nussler AK, Simmons RL, Billiar TR. A central role for IL-1 beta in the in vitro and in vivo regulation of hepatic inducible nitric oxide synthase. IL-1 beta induces hepatic nitric oxide synthesis. J Immunol. 1995;155(10):4890-8.
[75] Obolenskaya MYu, Vanin AF, Mordvintcev PI, M?lsch A, Decker K. Epr evidence of nitric oxide production by the regenerating rat liver. Biochem Biophys Res Commun. 1994;202(1):571-6.
[76] Hortelano S, Dewez B, Genaro AM, D?az-Guerra MJ, Bosc? L. Nitric oxide is released in regenerating liver after partial hepatectomy. Hepatology. 1995;21(3):776-86.
[77] Obolenskaya M, Schulze-Specking A, Plaumann B, Frenzer K, Freudenberg N, Decker K. Nitric oxide production by cells isolated from regenerating rat liver. Biochem Biophys Res Commun. 1994;204(3):1305-11.
[78] Pober JS, Cotran RS. Cytokines and endothelial cell biology. Physiol Rev. 1990;70(2):427-51.
[79] Higashitsuji H, Arii S, Furutani M, Mise M, Monden K, Fujita S, Ishiguro S, Kitao T, Nakamura T, Nakayama H, et al. Expression of cytokine genes during liver regeneration after partial hepatectomy in rats. J Surg Res. 1995;58(3):267-74.
[80] Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994;15(2):74-80.
[81] Sobczak J, Tournier MF, Lotti AM, Duguet M. Gene expression in regenerating liver in relation to cell proliferation and stress. Eur J Biochem. 1989;180(1):49-53.
[82] Ito Y, Hayashi H, Taira M, Tatibana M, Tabata Y, Isono K. Depression of liver-specific gene expression in regenerating rat liver: a putative cause for liver dysfunction after hepatectomy. J Surg Res. 1991;51(2):143-7.
[83] Pater LV, Chripunov VA, Kvitnitskaya AB, Prima VI, Obolenskaya MYu, Platonov OM. The expression of protooncogenes c-myc and c-fos during the first cell cycle in regenerating rat liver. Biopolym Cell. 1994; 10(2):57-60.
[84] Cornell RP. Acute phase responses after acute liver injury by partial hepatectomy in rats as indicators of cytokine release. Hepatology. 1990;11(6):923-31.
[85] Obolenskaya M, Kelve M, Sazonova L. 2',5'-oligo(A)synthetase activity during early metabolism reorientation in regenerating rat liver. Biopolym Cell. 1997; 13(5):391-6.
[86] Kanner J, Harel S, Granit R. Nitric oxide, an inhibitor of lipid oxidation by lipoxygenase, cyclooxygenase and hemoglobin. Lipids. 1992;27(1):46-9.
[87] Callery MP, Kamei T, Flye MW. Kupffer cell tumor necrosis factor-alpha production is suppressed during liver regeneration. J Surg Res. 1991;50(5):515-9.
[88] Goss JA, Mangino MJ, Callery MP, Flye MW. Prostaglandin E2 downregulates Kupffer cell production of IL-1 and IL-6 during hepatic regeneration. Am J Physiol. 1993;264(4 Pt 1):G601-8.
[89] Hashimoto N, Watanabe T, Toda G et al. Effects of prostaglandin on proliferation of hepatocytes in primary culture. Hepatology. 1990; 12:409.
[90] Holloway C, Seller J. Differential effects of PGE2 on proliferation of parenchymal and nonparenchymal cells: a possible mechanism of regulation in regenerating liver. Cells of Hepatic Sinusoid. 1997. 6. (in press).
[91] Bissell DM, Wang SS, Jarnagin WR, Roll FJ. Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation. J Clin Invest. 1995;96(1):447-55.
[92] Goureau O, Lepoivre M, Becquet F, Courtois Y. Differential regulation of inducible nitric oxide synthase by fibroblast growth factors and transforming growth factor beta in bovine retinal pigmented epithelial cells: inverse correlation with cellular proliferation. Proc Natl Acad Sci U S A. 1993;90(9):4276-80.
[93] Obolenskaia MIu, Gerasimova VV. [Role of complex-bound non-hemin iron in cell division]. Ukr Biokhim Zh. 1972;44(5):577-9.
[94] Holloway C, Sellar J. TGF and VEGF promote proliferation of Kupffer and sinusoidal endothelial cells in regenerating liver. Cells of Hepatic Sinusoid. 1997. 6. (in press).
[95] Stadler J, Harbrecht BG, Di Silvio M, Curran RD, Jordan ML, Simmons RL, Billiar TR. Endogenous nitric oxide inhibits the synthesis of cyclooxygenase products and interleukin-6 by rat Kupffer cells. J Leukoc Biol. 1993;53(2):165-72.
[96] Kan M, Huang JS, Mansson PE, Yasumitsu H, Carr B, McKeehan WL. Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration. Proc Natl Acad Sci U S A. 1989;86(19):7432-6.
[97] Mullhaupt B, Feren A, Fodor E, Jones A. Liver expression of epidermal growth factor RNA. Rapid increases in immediate-early phase of liver regeneration. J Biol Chem. 1994;269(31):19667-70.